Imaging immunomodulatory treatment responses in multiple sclerosis using hyperpolarized 13C metabolic magnetic resonance imaging

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Abstract

Abstract In recent years, the ability of conventional magnetic resonance imaging (MRI) to monitor high efficacy therapies and predict long-term disability in multiple sclerosis (MS) has been challenged. Here we used hyperpolarized 13C MR spectroscopy (MRS) metabolic imaging in a MS model of inflammatory-mediated demyelinating disease with widespread demyelination of the central nervous system (CNS). We showed that hyperpolarized metabolic imaging could monitor immune cell activation by measuring hyperpolarized [1-13C]pyruvate conversion to lactate and demonstrated that this approach detected response to two existing treatments, fingolimod and dimethyl fumarate. We observed a reduction of pyruvate-to-lactate flux after treatment, that can be explained by increased pyruvate dehydrogenase activity and decrease of immune cells. In addition, we evaluated brain perfusion using hyperpolarized [13C]urea, but saw no therapy effect. In conclusion, hyperpolarized magnetic resonance spectroscopy of [1-13C]pyruvate could provide a new non-invasive way to more directly detect immunological responses to disease-modifying therapies in MS and other diseases of the CNS.

Authors 5

1. Caroline Guglielmetti

   University of California, San Francisco

   Affiliation as printed

   University of California, San Francisco

   Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, CA, USA

   Department of Radiology and Biomedical Imaging, University of California San Francisco, CA, USA

2. Christian Cordano

   University of California, San Francisco

   Affiliation as printed

   University of California, San Francisco

   Department of Neurology, University of California San Francisco, CA, USA

3. Chloé Najac Aachen Department of Radiology C.J. Gorter Center for High Field MRI

   Leiden University Medical Center

   Affiliation as printed

   Leiden University Medical Center

   Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands

4. Ari Green

   University of California, San Francisco

   Affiliation as printed

   University of California, San Francisco

   Department of Neurology, University of California San Francisco, CA, USA

5. Myriam M. Chaumeil

   University of California, San Francisco

   Affiliation as printed

   University of California, San Francisco

   Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, CA, USA

   Department of Radiology and Biomedical Imaging, University of California San Francisco, CA, USA